{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T21:29:47Z","timestamp":1784064587278,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1614838"],"award-info":[{"award-number":["1614838"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Conservation is broadly used to identify biologically important (epi)genomic regions. In the case of tumor growth, preferential conservation of DNA methylation can be used to identify areas of particular functional importance to the tumor. However, reliable assessment of methylation conservation based on multiple tissue samples per patient requires the decomposition of methylation variation at multiple levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We developed a Bayesian hierarchical model that allows for variance decomposition of methylation on three levels: between-patient normal tissue variation, between-patient tumor-effect variation and within-patient tumor variation. We then defined a model-based conservation score to identify loci of reduced within-tumor methylation variation relative to between-patient variation. We fit the model to multi-sample methylation array data from 21 colorectal cancer (CRC) patients using a Monte Carlo Markov Chain algorithm (Stan). Sets of genes implicated in CRC tumorigenesis exhibited preferential conservation, demonstrating the model\u2019s ability to identify functionally relevant genes based on methylation conservation. A pathway analysis of preferentially conserved genes implicated several CRC relevant pathways and pathways related to neoantigen presentation and immune evasion. Our findings suggest that preferential methylation conservation may be used to identify novel gene targets that are not consistently mutated in CRC. The flexible structure makes the model amenable to the analysis of more complex multi-sample data structures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>The data underlying this article are available in the NCBI GEO Database, under accession code GSE166212. The R analysis code is available at https:\/\/github.com\/kevin-murgas\/DNAmethylation-hierarchicalmodel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab637","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T17:48:11Z","timestamp":1630950491000},"page":"22-29","source":"Crossref","is-referenced-by-count":8,"title":["A Bayesian hierarchical model to estimate DNA methylation conservation in colorectal tumors"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2893","authenticated-orcid":false,"given":"Kevin A","family":"Murgas","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, Stony Brook University School of Medicine , Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Public Health Genomics, University of Virginia , Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidea K","family":"Shahidi","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Duke University , Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Statistical Science, Duke University , Durham, NC 27708, USA"},{"name":"Department of Computer Science, Duke University , Durham, NC 27708, USA"},{"name":"Department of Mathematics, Duke University , Durham, NC 27708, USA"},{"name":"Department of Bioinformatics and Biostatistics, Duke University , Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, Duke University , Durham, NC 27710, USA"},{"name":"Duke Center for Statistical Genetics and Genomics, Duke University , Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc D","family":"Ryser","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Duke University , Durham, NC 27708, USA"},{"name":"Department of Population Health Sciences, Duke University Medical Center , Durham, NC 27701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"2023033101030461500_","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"2023033101030461500_","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/path.4132","article-title":"Whole-genome methylation analysis of benign and malignant colorectal tumours","volume":"229","author":"Beggs","year":"2013","journal-title":"J. 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